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Biomedical subjects

C Advenier

Publications and source records attributed to C Advenier.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effects of okadaic acid on the human isolated bronchus.

The effects of okadaic acid, a polyether derivative of a 38-carbon monocarboxylic fatty acid obtained from a culture of the marine dinoflagellate, Prorocentrum lima, were studied on the human isolated bronchus. In low concentrations (0.01 and 0.03 microM), okadaic acid had no significant effect of its own on the human isolated bronchus, but in higher concentrations (0.1-10 microM) it induced a series of contractions and relaxations. The first contraction was of low intensity (5% of maximum response to acetylcholine 3 mM) and occurred early. The second contraction had a higher amplitude (30% of maximum response to acetylcholine 3 mM) and reached its peak with okadaic acid 0.3 microM. At higher concentrations (1-10 microM), following a relaxation phase, a later rebound contraction occurred between 70 and 120 min and corresponded to 40% of the maximum response to acetylcholine 3 mM. In addition, okadaic acid inhibited or abolished the contractile response evoked by either KCl 60 mM or acetylcholine 3 mM with IC50 of 0.04 and 0.12 microM, respectively. The second contraction evoked by 0.3 microM okadaic acid was partially inhibited in the presence of the Ca2+ channel blocker, nicardipine 1 microM, or after incubation of the human bronchus in a Ca(2+)-free solution and it was completely abolished in the presence of CdSO4 0.1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium.

The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10(-3) M EGTA. Okadaic acid (5 x 10(-6) to 5 x 10(-5) M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 x 10(-5) M, to 142.3 +/- 6.1% (n = 7) of the contraction induced by oxytocin 10(-6) M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca(2+)-free medium containing 10(-3) M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M) significantly reduced, in a Ca(2+)-containing medium, the maximum contractile effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium, theophylline 3 x 10(-3) M and caffeine 10(-2) M did not modify the maximum effect of OA 10(-5) M but shortened the time to peak tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Neurotensin modulates cholinergic and noncholinergic neurotransmission in guinea-pig main bronchi in vitro.

Guinea-pig main bronchi were stimulated transmurally in vitro by electrical field stimulation in the presence of indomethacin 10(-6) M, propranolol 10(-6) M and phosphoramidon 10(-5) M. Two contractile neurogenic responses were successively observed. The second noncholinergic contraction was concentration dependently inhibited or abolished by neurotensin whereas the first cholinergic contraction was only partially inhibited. SR 48692, a novel antagonist of neurotensin receptors, reduced the inhibition induced by neurotensin (pKB = 9.75) whereas levocabastine, an antagonist of low-affinity neurotensin receptors, did not significantly modify the inhibitory effects of neurotensin on both neurally-mediated contractions. These results demonstrate that neurotensin exerts an inhibitory effect on neurotransmission in guinea-pig airways. Furthermore, the present study shows that the newly developed neurotensin receptors antagonist, SR 48692, is a potent inhibitor of the neurotensin inhibitory effects on cholinergic and noncholinergic contractions induced by electrical field stimulation of the guinea-pig isolated main bronchus.

Acetylcholine↗
PubMed1994

The nicardipine-isoprenaline interaction in human and guinea-pig isolated airways.

The effects of the dihydropyridine calcium antagonist nicardipine on the concentration-response curves of relaxant compounds acting through the adenylate-cyclase/cAMP system (isoprenaline, forskolin, adenosine and theophylline) or by the cGMP pathway (sodium nitroprusside) were studied on human isolated bronchus and guinea-pig isolated trachea. These effects were compared with those of nifedipine (a dihydropyridine derivative) and theophylline (a non-selective phosphodiesterase inhibitor). Nicardipine, in the range of 0.01 to 1 microM, significantly potentiated the relaxant effects of isoprenaline, forskolin, adenosine and theophylline, whereas the effects of sodium nitroprusside were significantly potentiated at 10 microM only. These results suggest that nicardipine behaves as an inhibitor of phosphodiesterases III and IV. One such effect may be involved in the potentiation of the isoprenaline relaxation of human and guinea-pig isolated airways.

Adenosine↗
PubMed1994

Effects of SR 48968 on the neuropeptide gamma-induced contraction of the human isolated bronchus.

Neuropeptide gamma (NP gamma) induced a contractile response of the human isolated bronchus which was potentiated by the neutral endopeptidase inhibitor, phosphoramidon, but was not modified by atropine and indomethacin. NP gamma was 3.31-fold more potent than NKA. Contractile response curves to NP gamma were shifted to the right and maximal responses reduced by the non-peptide NK2-receptor antagonist, SR 48968. The pKB of SR 48968 (8.94 +/- 0.18, n = 15), calculated according to Kenakin (1987) was very close to that reported for [Nle10]-NKA (4-10), a specific agonist of neurokinin NK2-receptors (8.86 +/- 0.13, n = 13), suggesting that the contractile effects of NP gamma on the human isolated bronchus were mediated through NK2A-receptors.

Benzamides↗
PubMed1994

Contractile effects of bradykinin on the isolated human small bronchus.

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.

Acetylcholine↗
PubMed1994

Rolipram, but not siguazodan or zaprinast, inhibits the excitatory noncholinergic neurotransmission in guinea-pig bronchi.

Theophylline has been reported to inhibit excitatory noncholinergic but not cholinergic-neurotransmission in guinea-pig bronchi. As theophylline might exert this effect through an inhibition of phosphodiesterases (PDE), and since many types of PDE have now been described, the aim of this study was to investigate the effects of three specific inhibitors of PDE on the electrical field stimulation (EFS) of the guinea-pig isolated main bronchus in vitro. The drugs used were siguazodan, rolipram and zaprinast, which specifically inhibit PDE types, III, IV and V, respectively. Guinea-pig bronchi were stimulated transmurally with biphasic pulses (16 Hz, 1 ms, 320 mA for 10 s) in the presence of indomethacin 10(-6) M and propranolol 10(-6) M. Two successive contractile responses were observed: a rapid cholinergic contraction, followed by a long-lasting contraction due to a local release of neuropeptides from C-fibre endings. Rolipram (10(-9) to 10(-6) M) but not siguazodan or zaprinast, inhibited the peptidergic contraction in a concentration-dependent manner. Conversely, the cholinergic response was unaffected. Contractile responses induced by exogenous acetylcholine (10(-8) to 10(-3) M) or [Nle10]NKA(4-10) (10(-10) to 10(-6) M) were also unaffected by rolipram, siguazodan and zaprinast (10(-7) M). These results demonstrate that concentrations of rolipram, similar to those which inhibit PDE, reduce the release of sensory neuropeptides from C-fibre endings, and suggest that the cyclic adenosine monophosphate (AMP) PDE type IV is specifically involved in this effect, as in other anti-inflammatory effects.

Animals↗
PubMed1994

Beta 3-adrenoceptor agonists, BRL 37344 and SR 58611A, do not induce relaxation of human, sheep and guinea-pig airway smooth muscle in vitro.

The existence of atypical- or beta 3-adrenoceptors has now been generally accepted. These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations. A recent study reported that beta 3-adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species. We investigated the in vitro responses of guinea-pig, human and sheep bronchial smooth muscle to isoprenaline, salbutamol (a selective beta 2-adrenoceptor agonist), and BRL 37344 and SR 58611A (two presumably selective beta 3-adrenoceptor agonists). The preparations were precontracted to 60-70% of maximal tension with histamine 10(-6) M for guinea-pig and human bronchi, or acetylcholine 10(-6) M for sheep bronchi. In each species, SR 58611A produced a slight fall in tension of about 10% of the effects of theophylline (3 mM), but this decrease in tension was not significantly different from the spontaneous and weak relaxation observed with saline addition during the same duration of the experiment. These relaxations were not modified by either the nonselective beta-adrenoceptor antagonist propranolol or the selective beta 2-adrenoceptor antagonist ICI 118,551. In contrast, BRL 37344 induced a significant concentration-dependent fall in tension induced by both spasmogens. Its relaxant effects were inhibited both by propranolol and ICI 118,551 in human and guinea-pig airways, whereas on the isolated sheep bronchus BRL 37344-induced relaxations were only slightly, albeit significantly, reduced with either of the beta-adrenoceptor antagonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1994

Relaxant effects and durations of action of formoterol and salmeterol on the isolated human bronchus.

The objective of this study was to evaluate the potency and efficacy (intrinsic activity) of formoterol and salmeterol and their duration of action in comparison with other beta-adrenoceptor agonists in isolated human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Potency (-log of the concentration of drug inducing 50% of maximal relaxation (-log EC50)) and efficacy (maximal effect (Emax), % of response to theophylline 3 x 10(-3) mol.l-1) were determined by analysis of cumulative isometric concentration-response curves to beta 2-adrenoceptor agonists in bronchial rings at resting tone or contracted maximally with acetylcholine 10(-3) mol.l-1 to induce functional antagonism. The onset and duration of action of beta-adrenoceptor agonists were measured by assessing the relaxant activity of drugs on the basal tone of isolated bronchi. In terms of potency, the rank order of the substances studied was formoterol > fenoterol > or = salmeterol > or = isoprenaline > or = salbutamol > or = adrenaline > or = terbutaline. Formoterol was 150-200 times more potent than isoprenaline. On preparations contracted with acetylcholine 10(-3) mol.l-1 the intrinsic activity (IA) of salbutamol, terbutaline and salmeterol compared with that of isoprenaline ranged 0.62-0.66. Intrinsic activity was higher with formoterol (0.84) and fenoterol (0.75). The onset of action of formoterol (2.14 +/- 0.55 min, n = 11) was not significantly different from that of salbutamol (1.90 +/- 0.24 min, n = 8) but shorter than that of salmeterol (6.40 +/- 1.40 min, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1993

Effects of sensitization on vasoactive intestinal polypeptide-induced relaxation and its concentration and binding in guinea-pig airways.

We investigated the relaxant effect of vasoactive intestinal polypeptide (VIP) in trachea and lung parenchyma from normal and sensitized guinea-pigs. A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings was used. In intact trachea, concentration-response curves for VIP entering from the mucosal surface (pD2 = 6.61 +/- 0.06) were displaced to the right compared with those for adventitial entry (pD2 = 6.78 +/- 0.04). Epithelium removal produced a leftward shift (approximately 2.8-fold) in the mucosal VIP concentration-response curve. Sensitization did not alter the responsiveness (maximal effect) or sensitivity (pD2 values) of tracheal rings to VIP irrespective of the surface of drug entry and of the absence or presence of epithelium. VIP-induced relaxation of normal and sensitized lung strips was also similar. Sensitization resulted in a significant decrease in tracheal VIP content (from 2.16 +/- 0.07 in normal to 0.60 +/- 0.08 nmol/mg protein in sensitized trachea; P < 0.05; n = 7) whereas the affinity of both high- and low-affinity binding sites for VIP increased as compared to that of normal trachea. Differences were not found in the binding capacities of normal and sensitized trachea. VIP content and binding did not differ in normal and sensitized lung. In conclusion, immunological sensitization produced changes in VIP tracheal content and binding but neither VIP-induced relaxation of isolated airways nor the influence of epithelium in this response was altered.

Animals↗
PubMed1993

Antitussive effect of SR 48968, a non-peptide tachykinin NK2 receptor antagonist.

The antitussive effects of SR 48968, a non-peptide tachykinin NK2 receptor antagonist, were investigated on citric acid-induced cough in the unanesthetized guinea-pig and compared with the effects of codeine. SR 48968 (0.01-0.3 mg/kg i.p.) inhibited in a dose-dependent manner the number of coughs induced by inhalation of an aqueous solution of citric acid with an ED50 of 0.1 mg/kg (0.17 mumol/kg). Under similar conditions, the codeine ED50 was 8 mg/kg (27 mumol/kg). Naloxone, an opioid receptor antagonist, abolished the effects of codeine but did not modify the effects of SR 48968. These data suggest that NK2 receptor stimulation might play an important role in the regulation of the cough reflex and that SR 48968 could be a potential antitussive agent.

Animals↗
PubMed1993

Inhibition of cholinergic neurotransmission in isolated guinea-pig main bronchi by SR 48968.

SR 48968 (10(-6) to 10(-5) M) inhibited the cholinergic response of the isolated guinea-pig main bronchus to electrical field stimulation. Since this effect was reversed by naloxone 10(-5) M and since SR 48968 had no effect on the contractile response to exogenous acetylcholine, we conclude that SR 48968 acts at a prejunctional level and that opioid receptors are involved. This effect was observed at concentrations approximately 75,000 times higher than those needed for blockade of tachykinin NK2 receptors.

Animals↗
PubMed1993

Effects of cromakalim on bradykinin-, histamine- and substance P-induced airway microvascular leakage in the guinea-pig.

The effects of cromakalim on the increase in microvascular permeability induced by histamine, substance P or bradykinin in guinea-pig airways were studied in vivo. Extravasation of i.v. injected Evans blue dye was used as an index of permeability. We also studied the effects of cromakalim on the contractile effect of substance P, histamine or bradykinin on the isolated guinea-pig main bronchus and on the contractile response of isolated guinea-pig main bronchi to electrical field stimulation. Cromakalim (30 to 300 micrograms.kg-1) did not inhibit the increase in microvascular permeability induced by histamine (30 micrograms.kg-1) in guinea-pig airways and potentiated (30 and 100 micrograms.kg-1) the effects of substance P (0.3 microgram.kg-1) in trachea, main bronchi and proximal intrapulmonary airways. In contrast, cromakalim (30 and 300 micrograms.kg-1) reduced the increase in microvascular permeability induced by bradykinin (0.3 microgram.kg-1). However, a significant potentiation of the effects of bradykinin was observed with cromakalim (100 micrograms.kg-1) in main bronchi and intrapulmonary airways. In the isolated guinea-pig main bronchus, the contractile effects of bradykinin, histamine and substance P were not modified by cromakalim (10(-5) M). Conversely, cromakalim (10(-5) M) significantly reduced both cholinergic and noncholinergic contractile responses induced by electrical field stimulation of the isolated guinea-pig main bronchus. In conclusion, cromakalim can partially inhibit the increase in microvascular permeability induced by i.v. bradykinin. It is suggested that this effect might occur through inhibition of the nonadrenergic noncholinergic excitatory (NANC) nerves preventing release by bradykinin of inflammatory neuropeptides such as substance P.

Animals↗
PubMed1993

Effects of three K+ channel openers on airways and pulmonary circulation in the isolated guinea-pig lung.

The antispasmodic and spasmolytic effects of levcromakalim (BRL 38227), aprikalim (RP 52891) and pinacidil were investigated in airways and pulmonary vessels of the isolated guinea-pig perfused lung. In airways, the three drugs exhibited modest antispasmodic properties, and pinacidil was more potent than levcromakalim and aprikalim against the contractions induced by carbachol (0.001-10 microM) or K+ (5-50 mM). Whereas levcromakalim and aprikalim acted only at low concentrations of K+, the rightward shift of the K+ concentration-effect curve produced by pinacidil was observed at all K+ concentrations (5-50 mM), suggesting that a mechanism of action other than K+ channel opening is involved in the effects of pinacidil. Pinacidil (0.3-100 microM) had the greatest spasmolytic effect in airways precontracted by carbachol (0.3 microM). The three K+ channel openers were equipotent against the sustained contractions of airways induced by 25 or 30 mM K+ and their spasmolytic activity was more marked against contractions induced by low rather low than high K+ concentrations. Levcromakalim and aprikalim were more effective as relaxant than as antispasmodic drugs. In K(+)-precontracted pulmonary vessels, the relaxant activity of pinacidil and levcromakalim was more pronounced than that observed in airways, suggesting a vascular selectivity of these drugs.

Animals↗
PubMed1993

Effects of capsaicin, (+/-)-CP-96,345 and SR 48968 on the bradykinin-induced airways microvascular leakage in guinea-pigs.

The aim of this study was to demonstrate the involvement of neuropeptides in the increase in microvascular permeability induced by bradykinin in guinea-pig airways in vivo and to determine the type of receptor involved. Extravasation of intravenously injected Evans blue dye was used as an index of vascular permeability. Increase in plasma exudation induced by bradykinin (0.3 micrograms/kg, iv) was reduced or abolished by capsaicin (40 mg/kg, sc, 7 days before experiments), a drug which destroys neurokinins in the NANC nerve endings. (+/-)-CP-96,345 (3 mg/kg, iv), an antagonist of neurokinin NK1-receptors, abolished the increase of vascular permeability induced by bradykinin and reduced or abolished the effects of substance P (0.3 micrograms/kg, iv). The higher dose of (+/-)-CP-96,345 (10 mg/kg, iv) completely blocked the effects of substance P, but it did not modify those of neurokinin A (100 micrograms/kg, iv). In contrast, SR 48968 (0.1 and 0.3 mg/kg, iv), an antagonist of neurokinin NK2-receptors, reduced the increase of vascular permeability induced by neurokinin A without influencing the effects of bradykinin and substance P. These results demonstrate that a stimulation of the non-adrenergic non-cholinergic (NANC) nerves and a subsequent release of neuropeptides, especially of substance P, is involved in the effects of bradykinin.

Animals↗
PubMed1993

Effects of age and indomethacin on response and sensitivity of pulmonary artery to phenylephrine and to histamine in pigs.

The vasoconstrictor effects of phenylephrine and histamine were investigated in isolated strips of pulmonary arteries in pigs during ageing. Interactions between phenylephrine-induced responses and arachidonic acid derivatives were also studied by incubating the blood-vessels with indomethacin. Potency (pD2 values) and maximal effects (EmaxX) recorded in 5-week-old piglets (group I, n = 5) with phenylephrine [5.71 +/- 0.17 and 0.76 +/- 0.22 g/mg of dry tissue respectively (mean +/- SEM)] were similar to values found in 12-week-old animals (group 2, n = 5) (5.49 +/- 0.30 and 1.06 +/- 0.27 g/mg of dry tissue respectively). The sensitivity and responsiveness of tissues to this agonist were significantly reduced in 26-week-old mature pigs (group 3, n = 6) as indicated by the decrease in pD2 (3.91 +/- 0.23; P < 0.01) and Emax (0.27 +/- 0.13 g/mg of dry tissue; P < 0.05) values observed in this group. Histamine (10(-3) M)-induced maximal responses (Emax) were significantly higher in group 2 (2.23 +/- 0.49 g/mg) than in group 1 (0.85 +/- 0.11 g/mg; P < 0.05) and in group 3 (0.48 +/- 0.10 g/mg; P < 0.01). In 5-week-old animals, indomethacin (3 x 10(-5) M) significantly (P < 0.05) shifted the concentration-response curve to phenylephrine to the right (0.28 log. units) and depressed contractions to this drug as shown by the significant decrease of 39.5% (P < 0.05) in Emax. This cyclo-oxygenase inhibitor had no effect in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Effects of rolipram and siguazodan on the human isolated bronchus and their interaction with isoprenaline and sodium nitroprusside.

1 The effects of the selective inhibitors of cyclic AMP phosphodiesterase type IV (rolipram) and type III (siguazodan) and their interactions with isoprenaline and sodium nitroprusside have been studied in the human isolated bronchus. 2 On bronchi under resting tone rolipram was, in terms of potency (pD2 = 7.77 +/- 0.14, n = 8), very similar to isoprenaline (pD2 = 7.31 +/- 0.12, n = 12) and salbutamol (pD2 = 7.12 +/- 0.17, n = 10) and approximately 10 fold more potent than siguazodan (pD2 = 6.80 +/- 0.12, n = 6). In terms of efficacy (Emax, expressed as percentage of maximal effect induced by theophylline 3 mM), both rolipram and siguazodan were less efficient (Emax = 74 +/- 6.7%, n = 8 and 66 +/- 7.5%, n = 6, respectively) than isoprenaline (Emax = 98 +/- 0.4%, n = 12) and salbutamol (Emax = 83 +/- 2.4%, n = 10). 3 During precontraction induced by methacholine (3 x 10(-7) M) or acetylcholine (10(-3) M), concentration-response curves to rolipram and siguazodan were shifted to the right and maximal effects reduced. Rolipram was more potent than siguazodan and, in terms of efficacy, it was less active. 4. Rolipram 10(-8) and 10(-7) M but not siguazodan potentiated the effects of isoprenaline as shown by the shift to the left of the concentration-response curve to isoprenaline. Sodium nitroprusside-induced relaxation was not modified by either drug. 5. These results show that rolipram is a potent relaxant of the human isolated bronchus, potentiating the effects of beta-adrenoceptor stimulation and suggest that, as previously demonstrated in other species(guinea-pig, cow) (Tomkinson et al., 1993), there may be a connection between the beta2-adrenoceptor subtype, which predominate in human airway smooth muscle, and the cyclic AMP phosphodiesterase type IV.

Albuterol↗